<i>Aggregatibacter actinomycetemcomitans</i>: Virulence of its leukotoxin and association with aggressive periodontitis

Åberg, Carola Höglund; Kelk, Peyman; Johansson, Anders

doi:10.4161/21505594.2014.982428

Cited by 136 publications

(95 citation statements)

References 84 publications

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“…Despite earlier studies reporting positive clinical results following treatment of this disease with mechanical debridement alone (Saxen et al, 1986), this regimen has resulted in certain limitations, especially regarding the control of invading and highly pathogenic microorganisms on oral tissues, such as the Aggregatibacter actinomycetemcomitans ( Aa ) (Meyer et al, 1996, Christersson et al, 1985, Xajigeorgiou et al, Christersson and Zambon, 1993, Herbert et al, 2015, Aberg et al, 2015). Thus, the combination of mechanical treatment with adjunctive Abx has been suggested in the treatment of aggressive periodontitis in an attempt to successfully reduce pathogenic bacteria, especially Aa , which has been long and strongly associated with this disease (Darby and Curtis, 2001), including in the population studied here (Shaddox et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Long‐term clinical response to treatment and maintenance of localized aggressive periodontitis: a cohort study

Miller

Branco-de-Almeida

Wolf

et al. 2016

J Clinic Periodontology

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Aim To evaluate long-term clinical response to periodontal therapy and maintenance in localized aggressive periodontitis (LAP). Materials and Methods One hundred forty-one African-Americans diagnosed with LAP, aged 5–25 years, were enrolled. Patients underwent periodontal mechanical debridement plus one week of amoxicillin/metronidazole. Mechanical therapy was repeated as needed and clinical parameters were recorded at baseline, 3, 6, 12, 18, and 24 months, and 2 additional annual follow-up visits after treatment. Radiographs from primary dentition of patients with LAP in permanent dentition, and additional healthy siblings (HS) were analyzed retrospectively. Results Periodontal therapy significantly improved probing depth and clinical attachment level up to 4 years (mean reductions: 2.18 ± 1.03 and 2.80 ± 1.43 mm, respectively). Percentage of affected sites was reduced at all timepoints and maintained up to 4 years. Noncompliance with antibiotics/appointments negatively affected the treatment response. Ninety percent of LAP patients in permanent dentition and 32% of HS presented radiographic bone loss in primary dentition. Conclusions Mechanical debridement with one-week of systemic antibiotics along with proper periodontal maintenance was effective in the treatment and successful maintenance of LAP for up to 4 years. LAP in permanent dentition may be preceded in the primary dentition. Clinicaltrials.gov #NCT01330719.

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Section: Introductionmentioning

confidence: 99%

Long‐term clinical response to treatment and maintenance of localized aggressive periodontitis: a cohort study

Miller

Branco-de-Almeida

Wolf

et al. 2016

J Clinic Periodontology

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“…Leukotoxins belong to the RTX toxin family, broadly distributed among Gram-negative bacteria and with diverse biological functions. Leukotoxins produced by the periodontal pathobiont Aggregatibacter actinomycetemcomitans are lethal to human monocytes and human T lymphocytes in vitro (73,74) and are a main virulence factor within deep periodontal pockets in aggressive periodontitis (75)(76)(77). Genes encoding other RTX family homologues include the gene coding for adenylate cyclase/hemolysin, which is the major virulence factor of Bordetella (78-80), as well as genes involved in an outer membrane translocation complex involved in RTX protein processing and export (76).…”

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confidence: 99%

Insights into the Evolution of Host Association through the Isolation and Characterization of a Novel Human Periodontal Pathobiont,Desulfobulbus oralis

Cross

Chirania

Xiong

et al. 2018

mBio

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The human oral microbiota encompasses representatives of many bacterial lineages that have not yet been cultured. Here we describe the isolation and characterization of previously uncultured Desulfobulbus oralis, the first humanassociated representative of its genus. As mammalian-associated microbes rarely have free-living close relatives, D. oralis provides opportunities to study how bacteria adapt and evolve within a host. This sulfate-reducing deltaproteobacterium has adapted to the human oral subgingival niche by curtailing its physiological repertoire, losing some biosynthetic abilities and metabolic independence, and by dramatically reducing environmental sensing and signaling capabilities. The genes that enable free-living Desulfobulbus to synthesize the potent neurotoxin methylmercury were also lost by D. oralis, a notably positive outcome of host association. However, horizontal gene acquisitions from other members of the microbiota provided novel mechanisms of interaction with the human host, including toxins like leukotoxin and hemolysins. Proteomic and transcriptomic analysis revealed that most of those factors are actively expressed, including in the subgingival environment, and some are secreted. Similar to other known oral pathobionts, D. oralis can trigger a proinflammatory response in oral epithelial cells, suggesting a direct role in the development of periodontal disease.IMPORTANCE Animal-associated microbiota likely assembled as a result of numerous independent colonization events by free-living microbes followed by coevolution with their host and other microbes. Through specific adaptation to various body sites and physiological niches, microbes have a wide range of contributions, from beneficial to disease causing. Desulfobulbus oralis provides insights into genomic and physiological transformations associated with transition from an open environment to a host-dependent lifestyle and the emergence of pathogenicity. Through a multifaceted mechanism triggering a proinflammatory response, D. oralis is a novel periodontal pathobiont. Even though culture-independent approaches can provide insights into the potential role of the human microbiome "dark matter," cultivation and experimental characterization remain important to studying the roles of individual organisms in health and disease.KEYWORDS evolution, genome analysis, oral microbiology, periodontitis, proteomics

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“…In addition to forming a protective biofilm, A. actinomycetemcomitans has many virulence factors, including secreted toxins, such as leukotoxin and cytolethal distending toxin (for reviews, see refs [13,14]. ), which harm host tissues and defense systems.…”

Section: Introductionmentioning

confidence: 99%

Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake

et al. 2018

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Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43 nM in static settings and 2.4 μM in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested β-lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.

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Aggregatibacter actinomycetemcomitans: Virulence of its leukotoxin and association with aggressive periodontitis

Cited by 136 publications

References 84 publications

Long‐term clinical response to treatment and maintenance of localized aggressive periodontitis: a cohort study

Long‐term clinical response to treatment and maintenance of localized aggressive periodontitis: a cohort study

Insights into the Evolution of Host Association through the Isolation and Characterization of a Novel Human Periodontal Pathobiont,Desulfobulbus oralis

Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake

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